{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:17:17Z","timestamp":1790770637099,"version":"4.1.0"},"reference-count":48,"publisher":"American Society for Cell Biology (ASCB)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:p>Motility, chemotaxis, and the acrosome reaction of animal sperm are all regulated by cyclic nucleotides and protein phosphorylation. One of the cyclic AMP-dependent protein kinase (PKA) substrates in sea urchin sperm is a member of the phosphodiesterase (PDE) family. The molecular identity and in vivo function of this PDE remained unknown. Here we cloned and characterized this sea urchin sperm PDE (suPDE5), which is an ortholog of human PDE5. The recombinant catalytic domain of suPDE5 hydrolyzes only cyclic GMP (cGMP) and the activity is pH-dependent. Phospho-suPDE5 localizes mainly to sperm flagella and the phosphorylation increases when sperm contact the jelly layer surrounding eggs. In vitro dephosphorylation of suPDE5 decreases its activity by \u223c50%. PDE5 inhibitors such as Viagra block the activity of suPDE5 and increase sperm motility. This is the first PDE5 protein to be discovered in animal sperm. The data are consistent with the hypothesis that suPDE5 regulates cGMP levels in sperm, which in turn modulate sperm motility.<\/jats:p>","DOI":"10.1091\/mbc.e05-08-0820","type":"journal-article","created":{"date-parts":[[2005,10,20]],"date-time":"2005-10-20T13:47:32Z","timestamp":1129816052000},"page":"114-121","source":"Crossref","is-referenced-by-count":34,"title":["Cyclic GMP-specific Phosphodiesterase-5 Regulates Motility of Sea Urchin Spermatozoa"],"prefix":"10.1091","volume":"17","author":[{"given":"Yi-Hsien","family":"Su","sequence":"first","affiliation":[{"name":"Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093-0202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor D.","family":"Vacquier","sequence":"additional","affiliation":[{"name":"Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093-0202"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1076","reference":[{"key":"REF1","doi-asserted-by":"crossref","unstructured":"Baxendale, R. W., and Fraser, L. R. (2005). Mammalian sperm phosphodiesterases and their involvement in receptor-mediated cell signaling important for capacitation.Mol. Reprod. Dev.71, 495\u2013508.","DOI":"10.1002\/mrd.20265"},{"key":"REF2","doi-asserted-by":"crossref","unstructured":"Beavo, J. A. (1995). Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms.Physiol. Rev.75, 725\u2013748.","DOI":"10.1152\/physrev.1995.75.4.725"},{"key":"REF3","doi-asserted-by":"crossref","unstructured":"B\u00f6hmer, M., Van, Q., Weyland, I., Hagen, V., Beyermann, M., Matsumoto, M., Hoshi, M., Hildebrand, E., and Kaupp, U. B. (2005). Ca2+spikes in the flagellum control chemotactic behavior of sperm.EMBO J.24, 2741\u20132752.","DOI":"10.1038\/sj.emboj.7600744"},{"key":"REF4","doi-asserted-by":"crossref","unstructured":"Clapper, D. L., Davis, J. A., Lamothe, P. J., Patton, C., and Epel, D. (1985). Involvement of zinc in the regulation of pHi, motility, and acrosome reactions in sea urchin sperm.J. Cell Biol.100, 1817\u20131824.","DOI":"10.1083\/jcb.100.6.1817"},{"key":"REF5","doi-asserted-by":"crossref","unstructured":"Cook, S. P., and Babcock, D. F. (1993). Selective modulation by cGMP of the K+channel activated by speract.J. Biol. Chem.268, 22402\u201322407.","DOI":"10.1016\/S0021-9258(18)41543-8"},{"key":"REF6","doi-asserted-by":"crossref","unstructured":"Corbin, J. D., and Francis, S. H. (1999). Cyclic GMP phosphodiesterase-5, target of sildenafil.J. Biol. Chem.274, 13729\u201313732.","DOI":"10.1074\/jbc.274.20.13729"},{"key":"REF7","doi-asserted-by":"crossref","unstructured":"Corbin, J. D., Turko, I. V., Beasley, A., and Francis, S. H. (2000). Phosphorylation of phosphodiesterase-5 by cyclic nucleotide-dependent protein kinase alters its catalytic and allosteric cGMP-binding activities.Eur. J. Biochem.267, 2760\u20132767.","DOI":"10.1046\/j.1432-1327.2000.01297.x"},{"key":"REF8","doi-asserted-by":"crossref","unstructured":"Darszon, A., Beltr\u00e1n, C., Felix, R., Nishigaki, T., and Trevi\u00f1o, C. L. (2001). Ion transport in sperm signaling.Dev. Biol.240, 1\u201314.","DOI":"10.1006\/dbio.2001.0387"},{"key":"REF9","doi-asserted-by":"crossref","unstructured":"Darszon, A., Nishigaki, T., Wood, C., Trevi\u00f1o, C. L., Felix, R., and Beltr\u00e1n, C. (2005). Calcium channels and Ca2+fluctuations in sperm physiology.Int. Rev. Cytol.243, 79\u2013172.","DOI":"10.1016\/S0074-7696(05)43002-8"},{"key":"REF10","doi-asserted-by":"crossref","unstructured":"Deana, R., Foresta, C., Bonaga, G., and Rigoni, F. (1986). A simple nephelometric method for measuring the progressive motility and collecting motile spermatozoa.Andrologia18, 37\u201341.","DOI":"10.1111\/j.1439-0272.1986.tb01735.x"},{"key":"REF11","doi-asserted-by":"crossref","unstructured":"du Plessis, S. S., de Jongh, P. S., and Franken, D. R. (2004). Effect of acutein vivosildenafil citrate andin vitro8-bromo-cGMP treatments on semen parameters and sperm function.Fertil. Steril.81, 1026\u20131033.","DOI":"10.1016\/j.fertnstert.2003.09.054"},{"key":"REF12","doi-asserted-by":"crossref","unstructured":"Fawcett, L., Baxendale, R., Stacey, P., McGrouther, C., Harrow, I., Soderling, S., Hetman, J., Beavo, J. A., and Phillips, S. C. (2000). Molecular cloning and characterization of a distinct human phosphodiesterase gene family: PDE11A.Proc. Natl. Acad. Sci. USA97, 3702\u20133707.","DOI":"10.1073\/pnas.97.7.3702"},{"key":"REF13","doi-asserted-by":"crossref","unstructured":"Fisch, J. D., Behr, B., and Conti, M. (1998). Enhancement of motility and acrosome reaction in human spermatozoa: differential activation by type-specific phosphodiesterase inhibitors.Hum. Reprod.13, 1248\u20131254.","DOI":"10.1093\/humrep\/13.5.1248"},{"key":"REF14","doi-asserted-by":"crossref","unstructured":"Francis, S. H., Colbran, J. L., McAllister-Lucas, L. M., and Corbin, J. D. (1994). Zinc interactions and conserved motifs of the cGMP-binding cGMP-specific phosphodiesterase suggest that it is a zinc hydrolase.J. Biol. Chem.269, 22477\u201322480.","DOI":"10.1016\/S0021-9258(17)31669-1"},{"key":"REF15","doi-asserted-by":"crossref","unstructured":"Francis, S. H., Lincoln, T. M., and Corbin, J. D. (1980). Characterization of a novel cGMP binding protein from rat lung.J. Biol. Chem.255, 620\u2013626.","DOI":"10.1016\/S0021-9258(19)86221-X"},{"key":"REF16","doi-asserted-by":"crossref","unstructured":"Galindo, B. E., Beltr\u00e1n, C., Cragoe, E. J., Jr., and Darszon, A. (2000). Participation of a K+channel modulated directly by cGMP in the speract-induced signaling cascade ofStrongylocentrotus purpuratussea urchin sperm.Dev. Biol.221, 285\u2013294.","DOI":"10.1006\/dbio.2000.9678"},{"key":"REF17","doi-asserted-by":"crossref","unstructured":"Garbers, D. L. (1989). Molecular basis of fertilization.Annu. Rev. Biochem.58, 719\u2013742.","DOI":"10.1146\/annurev.bi.58.070189.003443"},{"key":"REF18","unstructured":"Garbers, D. L., and Kopf, G. S. (1980). The regulation of spermatozoa by calcium and cyclic nucleotides.Adv. Cyclic Nucleotide Res.13, 251\u2013306."},{"key":"REF19","doi-asserted-by":"crossref","unstructured":"Gatti, J. L., and Christen, R. (1985). Regulation of internal pH of sea urchin sperm. A role for the Na+\/K+pump.J. Biol. Chem.260, 7599\u20137602.","DOI":"10.1016\/S0021-9258(17)39650-3"},{"key":"REF20","doi-asserted-by":"crossref","unstructured":"Hetman, J. M., Robas, N., Baxendale, R., Fidock, M., Phillips, S. C., Soderling, S. H., and Beavo, J. A. (2000). Cloning and characterization of two splice variants of human phosphodiesterase 11A.Proc. Natl. Acad. Sci. USA97, 12891\u201312895.","DOI":"10.1073\/pnas.200355397"},{"key":"REF21","doi-asserted-by":"crossref","unstructured":"Hirohashi, N., and Vacquier, V. D. (2002). Egg sialoglycans increase intracellular pH and potentiate the acrosome reaction of sea urchin sperm.J. Biol. Chem.277, 8041\u20138047.","DOI":"10.1074\/jbc.M110661200"},{"key":"REF22","doi-asserted-by":"crossref","unstructured":"Kaupp, U. B., Solzin, J., Hildebrand, E., Brown, J. E., Helbig, A., Hagen, V., Beyermann, M., Pampaloni, F., and Weyand, I. (2003). The signal flow and motor response controlling chemotaxis of sea urchin sperm.Nat. Cell Biol.5, 109\u2013117.","DOI":"10.1038\/ncb915"},{"key":"REF23","doi-asserted-by":"crossref","unstructured":"Ke, H. (2004). Implications of PDE4 structure on inhibitor selectivity across PDE families.Int. J. Impot. Res.16(Suppl. 1), S24\u2013S27.","DOI":"10.1038\/sj.ijir.3901211"},{"key":"REF24","doi-asserted-by":"crossref","unstructured":"Kuwayama, H., Snippe, H., Derks, M., Roelofs, J., and Van Haastert, P. J. (2001). Identification and characterization of DdPDE3, a cGMP-selective phosphodiesterase fromDictyostelium.Biochem. J.353, 635\u2013644.","DOI":"10.1042\/bj3530635"},{"key":"REF25","doi-asserted-by":"crossref","unstructured":"Lefi\u00e8vre, L., De Lamirande, E., and Gagnon, C. (2000). The cyclic GMP-specific phosphodiesterase inhibitor, sildenafil, stimulates human sperm motility and capacitation but not acrosome reaction.J. Androl.21, 929\u2013937.","DOI":"10.1002\/j.1939-4640.2000.tb03424.x"},{"key":"REF26","doi-asserted-by":"crossref","unstructured":"Lefi\u00e8vre, L., de Lamirande, E., and Gagnon, C. (2002). Presence of cyclic nucleotide phosphodiesterases PDE1A, existing as a stable complex with calmodulin, and PDE3A in human spermatozoa.Biol. Reprod.67, 423\u2013430.","DOI":"10.1095\/biolreprod67.2.423"},{"key":"REF27","doi-asserted-by":"crossref","unstructured":"Loughney, K.et al.(1998). Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3\u2032,5\u2032-cyclic nucleotide phosphodiesterase.Gene216, 139\u2013147.","DOI":"10.1016\/S0378-1119(98)00303-5"},{"key":"REF28","unstructured":"Morisawa, M. (1994). Cell signaling mechanisms for sperm motility.Zoolog. Sci.11, 647\u2013662."},{"key":"REF29","doi-asserted-by":"crossref","unstructured":"Murthy, K. S. (2001). Activation of phosphodiesterase 5 and inhibition of guanylate cyclase by cGMP-dependent protein kinase in smooth muscle.Biochem. J.360, 199\u2013208.","DOI":"10.1042\/bj3600199"},{"key":"REF30","doi-asserted-by":"crossref","unstructured":"Neill, A. T., and Vacquier, V. D. (2004). Ligands and receptors mediating signal transduction in sea urchin spermatozoa.Reproduction127, 141\u2013149.","DOI":"10.1530\/rep.1.00085"},{"key":"REF31","doi-asserted-by":"crossref","unstructured":"Nishigaki, T., Zamundio, F. Z., Possani, L. D., and Darszon, A. (2001). Time-resolved responses to an egg peptide measured by stopped-flow fluorometry.Biochem. Biophys. Res. Commun.284, 531\u2013535.","DOI":"10.1006\/bbrc.2001.5000"},{"key":"REF32","doi-asserted-by":"crossref","unstructured":"Percival, M. D., Yeh, B., and Falgueyret, J. P. (1997). Zinc dependent activation of cAMP-specific phosphodiesterase (PDE4A).Biochem. Biophys. Res. Commun.241, 175\u2013180.","DOI":"10.1006\/bbrc.1997.7542"},{"key":"REF33","doi-asserted-by":"crossref","unstructured":"Richter, W., Dettmer, D., and Glander, H. (1999). Detection of mRNA transcripts of cyclic nucleotide phosphodiesterase subtypes in ejaculated human spermatozoa.Mol. Hum. Reprod.5, 732\u2013736.","DOI":"10.1093\/molehr\/5.8.732"},{"key":"REF34","doi-asserted-by":"crossref","unstructured":"Rybalkin, S. D., Rybalkina, I. G., Feil, R., Hofmann, F., and Beavo, J. A. (2002). Regulation of cGMP-specific phosphodiesterase (PDE5) phosphorylation in smooth muscle cells.J. Biol. Chem.277, 3310\u20133317.","DOI":"10.1074\/jbc.M106562200"},{"key":"REF35","doi-asserted-by":"crossref","unstructured":"Sano, M. (1976). Subcellular localizations of guanylate cyclase and 3\u2032,5\u2032-cyclic nucleotide phosphodiesterase in sea urchin sperm.Biochim. Biophys. Acta428, 525\u2013531.","DOI":"10.1016\/0304-4165(76)90061-1"},{"key":"REF36","doi-asserted-by":"crossref","unstructured":"Soderling, S. H., and Beavo, J. A. (2000). Regulation of cAMP and cGMP signaling: new phosphodiesterases and new functions.Curr. Opin. Cell Biol.12, 174\u2013179.","DOI":"10.1016\/S0955-0674(99)00073-3"},{"key":"REF37","doi-asserted-by":"crossref","unstructured":"Solzin, J., Van, Q., Brown, J. E., Hildebrand, E., Weyland, I., and Kaupp, U. B. (2004). Revisiting the role of H+ in chemotactic signaling of sperm.J. Gen. Physiol.124, 115\u2013124.","DOI":"10.1085\/jgp.200409030"},{"key":"REF38","doi-asserted-by":"crossref","unstructured":"Sonnenburg, W. K., Rybalkin, S. D., Bornfeldt, K. E., Kwak, K. S., Rybalkina, I. G., and Beavo, J. A. (1998). Identification, quantitation, and cellular localization of PDE1 calmodulin-stimulated cyclic nucleotide phosphodiesterases.Methods14, 3\u201319.","DOI":"10.1006\/meth.1997.0561"},{"key":"REF39","doi-asserted-by":"crossref","unstructured":"Su, Y. H., Chen, S. H., Zhou, H., and Vacquier, V. D. (2005). Tandem mass spectrometry identifies proteins phosphorylated by cyclic AMP dependent protein kinase when sea urchin sperm undergo the acrosome reaction.Dev. Biol.285, 116\u2013125.","DOI":"10.1016\/j.ydbio.2005.06.007"},{"key":"REF40","unstructured":"Swofford, D. L. (2002).PAUP*. Phylogenetic Analysis Using Parsimony (*and Other Methods), Version 4. Sunderland, MA: Sinauer Associates."},{"key":"REF41","doi-asserted-by":"crossref","unstructured":"Thomas, M. K., Francis, S. H., and Corbin, J. D. (1990). Characterization of a purified bovine lung cGMP-binding cGMP phosphodiesterase.J. Biol. Chem.265, 14964\u201314970.","DOI":"10.1016\/S0021-9258(18)77210-4"},{"key":"REF42","doi-asserted-by":"crossref","unstructured":"Toowicharanont, P., and Shapiro, B. M. (1988). Regional differentiation of the sea urchin sperm plasma membrane.J. Biol. Chem.263, 6877\u20136883.","DOI":"10.1016\/S0021-9258(18)68726-5"},{"key":"REF43","doi-asserted-by":"crossref","unstructured":"Vacquier, V. D., and Hirohashi, N. (2004). Sea urchin spermatozoa.Methods Cell Biol.74, 523\u2013544.","DOI":"10.1016\/S0091-679X(04)74021-2"},{"key":"REF44","doi-asserted-by":"crossref","unstructured":"Ward, G. E., Garbers, D. L., and Vacquier, V. D. (1985). Effects of extracellular egg factors on sperm guanylate cyclase.Science227, 768\u2013770.","DOI":"10.1126\/science.2857502"},{"key":"REF45","doi-asserted-by":"crossref","unstructured":"Wood, C. D., Darszon, A., and Whitaker, M. (2003). Speract induces calcium oscillations in the sperm tail.J. Cell Biol.161, 89\u2013101.","DOI":"10.1083\/jcb.200212053"},{"key":"REF46","doi-asserted-by":"crossref","unstructured":"Wood, C. D., Nishigaki, T., Furuta, T., Baba, S. A., and Darszon, A. (2005). Real-time analysis of the role of Ca2+in flagellar movement and motility in single sea urchin sperm.J. Cell Biol.169, 725\u2013731.","DOI":"10.1083\/jcb.200411001"},{"key":"REF47","doi-asserted-by":"crossref","unstructured":"Zhang, K. Y.et al.(2004). A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases.Mol. Cell15, 279\u2013286.","DOI":"10.1016\/j.molcel.2004.07.005"},{"key":"REF48","doi-asserted-by":"crossref","unstructured":"Zoraghi, R., Corbin, J. D., and Francis, S. H. (2004). Properties and functions of GAF domains in cyclic nucleotide phosphodiesterases and other proteins.Mol. Pharmacol.65, 267\u2013278.","DOI":"10.1124\/mol.65.2.267"}],"container-title":["Molecular Biology of the Cell"],"original-title":[],"language":"en","deposited":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T03:54:56Z","timestamp":1706673296000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.molbiolcell.org\/doi\/10.1091\/mbc.e05-08-0820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,1]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,1]]}},"alternative-id":["10.1091\/mbc.e05-08-0820"],"URL":"https:\/\/doi.org\/10.1091\/mbc.e05-08-0820","relation":{},"ISSN":["1059-1524","1939-4586"],"issn-type":[{"value":"1059-1524","type":"print"},{"value":"1939-4586","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,1]]}}}